QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
Acta Physiol (Oxf). 2017 Apr;219(4):803-813. doi: 10.1111/apha.12721. Epub 2016 Jun 27.
Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting.
Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis.
We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions.
Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.
运动训练被认为是一种非药物方法，可以预防癌症恶病质引起的骨骼肌消耗并改善肌肉功能。然而，对于这种有益作用的潜在机制知之甚少。在这项研究中，我们旨在首先探讨 TWEAK 信号通路在癌症引起的骨骼肌消耗中的作用，其次评估长期运动是否会改变 TWEAK 信号通路并预防肌肉消耗。
将雌性 Sprague-Dawley 大鼠随机分为对照组和运动组。每组各有 15 只动物接触 N-甲基-N-亚硝脲致癌剂。运动组的动物接受了 35 周的适度跑步机运动。实验结束后，处死动物并采集腓肠肌进行形态学和生化分析。
我们验证了运动训练可预防肿瘤诱导的骨骼肌 TWEAK/NF-κB 信号通路，从而对纤维横截面积和代谢产生有益影响。事实上，35 周的运动训练促进了 PGC-1α 和氧化磷酸化复合物的上调。在荷瘤动物中，这种运动引起的肌肉重塑与恶性乳腺病变较少有关。
数据支持积极生活方式对预防乳腺癌引起的肌肉消耗的益处，强调 TWEAK/NF-κB 信号通路作为维持肌肉质量的潜在治疗靶点。
